NGR005: Pilot Study of NGR-hTNF Administered at Low and High Doses in Combination With a Standard Oxaliplatin Based Regimen in Patients With Metastatic Colorectal Cancer

Inclusion Criteria:

- Patients ≥ 18 years with metastatic colorectal cancer (CRC) treated with no more than
three standard systemic regimens (including biologic agents) for metastatic disease

- Life expectancy more than 3 months

- ECOG Performance status 0-1

- Adequate baseline bone marrow, hepatic and renal function, defined as follows:

- Neutrophils >1.5 x 10^9/L and platelets > 100 x 10^9/L

- Bilirubin <1.5 x ULN

- AST and/or ALT <2.5 x ULN in absence of liver metastasis

- AST and/or ALT <5 x ULN in presence of liver metastasis

- Serum creatinine <1.5 x ULN

- Creatinine clearance (estimated according to Cockcroft-Gault formula) ≥ 50
ml/min

- Patients may have had prior therapy providing the following conditions are met:

- Chemotherapy, radiation therapy, hormonal therapy or immunotherapy: wash-out
period of 28 days before start treatment

- Surgery: wash-out period of 14 days before start treatment

- Patients must give written informed consent to participate in the study

Exclusion Criteria:

- Concurrent anticancer therapy

- Patients must not receive any other investigational agents while on study

- Patients with myocardial infarction within the last six (6) months, unstable angina,
New York Heart Association (NYHA) grade II or greater congestive heart failure, or
serious cardiac arrhythmia requiring medication

- Uncontrolled hypertension

- Prolonged QTc interval (congenital or acquired)

- Patient with significant peripheral vascular disease

- Clinical signs of CNS involvement

- Patients with active or uncontrolled systemic disease/infections or with serious
illness or medical conditions, which is incompatible with the protocol

- Symptomatic peripheral neuropathy ≥ grade 1 according the NCI CTCAE v.3.0.

- Known hypersensitivity/allergic reaction or contraindications to human albumin
preparations or to any of the excipients

- Known hypersensitivity/allergic reaction or contraindications to platinum compounds
or fluoropyrimidines

- Any psychological, familial, sociological or geographical condition potentially
hampering compliance with the study protocol

- Pregnancy or lactation.

- Patients - both males and females - with reproductive potential (i.e. menopausal for
less than 1-year and not surgically sterilized) must practice effective contraceptive
measures throughout the study.

- Women of childbearing potential must provide a negative pregnancy test (serum or
urine) within 14 days prior to registration